Early Onset Alzheimer's Disease is Associated with a Distinct Neuropsychological Profile

Abstract

Alzheimer's disease (AD) in younger patients is associated with a higher prevalence of atypical symptoms. We examined neuropsychological performance according to age-at-onset. We assessed cognition in 172 patients with AD (81 early and 91 late onset) in five cognitive domains (memory, language, visuo-spatial functioning, executive functioning, attention). Dementia severity was assessed using the Mini-Mental State Examination (MMSE) and global cognitive decline using Cambridge Cognitive Examination (CAMCOG). Analyses of variance were performed with age-at-onset as between-subjects factor, and gender and education as covariates. Analysis was repeated after stratification for dementia severity (based on median MMSE). In early onset AD, age (mean ± SD) was 60 ± 4 years; 44 (54%) were female. In late onset AD, age was 72 ± 5 years; 47 (52%) were female. Dementia severity and global cognitive decline did not differ between groups (early onset: MMSE: 20 ± 5, CAMCOG: 69 ± 15, late onset: MMSE: 21 ± 5, CAMCOG: 70 ± 15; p > 0.05). Early onset patients performed worse than late onset patients on visuo-spatial functioning (p < 0.01), executive functioning (p < 0.001), and attention (p < 0.01). Late onset patients performed worse on memory, although not significantly (p = 0.11). Stratification for dementia severity showed that in mildly demented early onset patients, memory function was remarkably preserved compared to late onset patients (p < 0.01). In moderate AD, differences in memory function disappeared, but early onset patients performed worse on visuo-spatial functioning (p < 0.01), executive functioning (p < 0.001), and attention (p < 0.01) than late onset patients. Adjustment for APOE left results unchanged. In conclusion, early onset AD presents with a different cognitive profile and the disease course seems different. Relative sparing of memory function in early stages stresses the need to adequately test other cognitive domains.

Early-onset and late-onset Alzheimer's disease are associated with distinct patterns of memory impairment

“…The subgroups of AD patients were classified based on a determined cut-off of 65 years of age at onset, based on previous studies comparing features of EOAD and LOAD patients (Kemp et al, 2003;Kim et al, 2005;Shiino et al, 2006;Frisoni et al, 2007;Rabinovici et al, 2010;Canu et al, 2012;Sa et al, 2012;Smits et al, 2012;Cho et al, 2013), as well as on clinical grounds (Amaducci et al, 1986). This cut-off is also used in the DSM-IV TR nomenclature to specify subtypes (American Psychiatric Association, 2000).…”

“…Several studies also found that language function was more altered in early-onset patients (Chui et al, 1985;Filley et al, 1986;Becker et al, 1988;Faber-Langendoen et al, 1988;Binetti et al, 1996;Imamura et al, 1998), even when factors such as education and severity of dementia were controlled for, while variable findings were reported regarding the presence of apraxia (Seltzer and Sherwin, 1983;Reid et al, 1996). A more recent neuropsychological study reported that mildly demented EOAD patients performed worse than LOAD patients on visuospatial functioning, executive functioning, and attention, while memory was remarkably preserved (Smits et al, 2012). Other studies have also reported that early-onset patients have significant visuospatial difficulties when compared to late-onset patients Koedam et al, 2010).…”

“…Several studies did not find any distinctive differences between EOAD and LOAD patients (Cummings et al, 1985;Bayles et al, 1987;Grady et al, 1987;Selnes et al, 1988;Toyota et al, 2007) or have attributed such differences to dementia severity (Jacobs et al, 1994;Smits et al, 2012). Regarding memory, a relative sparing of memory in EOAD has been reported (Binetti et al, 1996;Smits et al, 2012), while several studies have found that LOAD patients present primarily with memory difficulties (Jacobs et al, 1994;Imamura et al, 1998).…”

“…Regarding memory, a relative sparing of memory in EOAD has been reported (Binetti et al, 1996;Smits et al, 2012), while several studies have found that LOAD patients present primarily with memory difficulties (Jacobs et al, 1994;Imamura et al, 1998). Several studies also found that language function was more altered in early-onset patients (Chui et al, 1985;Filley et al, 1986;Becker et al, 1988;Faber-Langendoen et al, 1988;Binetti et al, 1996;Imamura et al, 1998), even when factors such as education and severity of dementia were controlled for, while variable findings were reported regarding the presence of apraxia (Seltzer and Sherwin, 1983;Reid et al, 1996).…”

“…In summary, there have been conflicting results in the literature regarding the patterns of cognitive dysfunction in EOAD and LOAD, but taken together results of these studies seem to suggest that EOAD patients have more prominent difficulties in non-memory domains which include language, visuospatial skills, and executive functions. The absence of consensus may be due to several factors: 1) cognitive evaluations of EOAD and LOAD patients in previous studies were often brief and limited to general domains such as memory and executive functions, while other domains were often not tested (Smits et al, 2012); 2) differences in disease stage may not have been taken into account; 3) variability in the tests used to evaluate specific cognitive domains; 4) specific subdomains were not considered (e.g. memory), possibly eluding differences between EOAD and LOAD groups.…”